6-64611796-A-G

Position:

• chr6-64611796-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142800.2(EYS):​c.3684+5622T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,088 control chromosomes in the GnomAD database, including 50,457 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (50457 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254

Genes affected

EYS (HGNC:21555): (eyes shut homolog) The product of this gene contains multiple epidermal growth factor (EGF)-like and LamG domains. The protein is expressed in the photoreceptor layer of the retina, and the gene is mutated in autosomal recessive retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYS	NM_001142800.2	c.3684+5622T>C		intron_variant		ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.3684+5622T>C		intron_variant			NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.3684+5622T>C		intron_variant		5	NM_001142800.2	ENSP00000424243	A2
EYS	ENST00000370621.7	c.3684+5622T>C		intron_variant		1		ENSP00000359655	P2
EYS	ENST00000330816.5	n.305+5622T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122942 AN: 151970 Hom.: 50392 Cov.: 32

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.756

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.809 AC: 123066 AN: 152088 Hom.: 50457 Cov.: 32 AF XY: 0.809 AC XY: 60098 AN XY: 74324

Gnomad4 AFR AF: 0.951

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.837

Gnomad4 FIN AF: 0.744

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.758

Alfa AF: 0.759 Hom.: 17369

Bravo AF: 0.818

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.6
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs604490; hg19: chr6-65321689;